Registration Dossier

Administrative data

Description of key information

Oral (OECD TG 401), rat: LD50 > 2007 mg/kg bw (limit test)

Dermal: (OCED TG 402), rat: LD50 > 2007 mg/kg bw (limit test)

Inhalation (OCED TG 403), rat, 4 h exposure: LC50 > 13500 mg/m³ (limit test).

It was not stated whether the tested concentration was the highest achievable concentration, but taken into account the molecular weight (178.3 g/mol) and the vapour pressure of the test substance (100 Pa at 25 °C and 1013 hPa) a saturated vapour concentration of 7190 mg/m³ (7.19 mg/L) can be calculated. It is therefore assumed that the tested concentration was the highest achievable dose in the test atmosphere and a higher exposure concentration is unlikely.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16.09.1991 to 13.03.1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Iffa-Crédo, FRANCE
- Age at study initiation: 5-7 wk
- Weight at study initiation: 136-228 g
- Fasting period before study: 17-18 hr
- Housing: 5/cage (separate sexes), polycarbonate cages
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): at least 8
- Photoperiod (hrs dark / hrs light): 12 h/12 h

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
none

MAXIMUM DOSE VOLUME APPLIED: 2.23 ml/kg bw
Doses:
main study: 2007 mg/kg bw
preliminary study: 504, 1008, 2007 mg/kg bw
No. of animals per sex per dose:
main study: 5
preliminary study: 2
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (changes to skin and fur, eyes, mucous membranes, respiratory system, circulatory system, autonomic and central nervous system, as well as somato-motor activity and behaviour. Shivering, convulsions, salivation, diarrhoea, lethargy, sleeping and coma were noted with particular attention.)
- Frequency of observations and weighing: deaths and abnormal clinical signs were noted 15 minutes after administration, then 1, 2 and 4 h then daily for 14 days; weighed on day before treatment (day -1), immediately prior to administration of the test substance (day 1), and on Days 8 and 15.
- Necropsy of survivors performed: yes, after the 14 day observation period (Day 15), with particular attention paid to the following organs: liver, heart, kidneys and lungs.
Statistics:
The body weights of the animals were evaluated for each sex. The mean, standard deviation and coefficient of variation were calculated. There were no deaths so an LD50 could not be calculated.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 007 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No deaths at any dose.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 007 mg/kg bw
Based on:
test mat.
Mortality:
No deaths throughout the study.
Clinical signs:
Main study (2007 mg/kg bw)
Subdued behaviour in all treated animals at 1, 2 and 4 h, no overt clinical effects at Day 2.
Body weight:
No effect.
Gross pathology:
No remarkable macroscopic findings.

Table 1: Number of animals dead

 

Dose
(mg/kg bw)

Mortality (dead/total)

Male

Female

Combined

504a

0/2

0/2

0/4

1008a

0/2

0/2

0/4

2007a

0/2

0/2

0/4

2007b

0/5

0/5

0/10

a. preliminary study

b. main study

Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
In an acute oral limit test, conducted in compliance with the now deleted OECD 401 and in accordance with GLP (reliability score 1), there was no mortality or marked systemic effect in rats at 2007 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 007 mg/kg bw
Quality of whole database:
This study was conducted according to an appropriate OECD test guideline and in compliance with GLP.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 3 Sept to 17 Sept 1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
the determination of the particle size failed, presumably because the substance was emitted mainly as vapour
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
It was technically not possible to determine the particle size, necropsy was performed but a detailed description of its extend is missing.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Hoechst AG, SPF-Zucht, GERMANY
- Age at study initiation: 8-10 wk
- Weight at study initiation: males 188 (184-191) g; females 190 (185-200) g
- Housing: 1/plastic cage
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 50 +/- 20
- Photoperiod (hrs dark / hrs light): 12h/ 12 h

IN-LIFE DATES: From: 1991-09-03 To: 1991-09-17
Route of administration:
other: aerosol/vapour
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
[from report in German]
- Exposure apparatus: cylindrical plastic cages housed in stainless steel inhalation chamber
- Exposure chamber volume: total volume 60 L
- Method of holding animals in test chamber: rats were fitted into test tubes with a coned end reaching into the test chamber
- Source and rate of air: 800 L/h
- Method of conditioning air: air was led at a constant pressure of 4 bar into a nozzle and through separators and filters
- System of generating particulates/aerosols: test substance was injected contineously into the air flow in the nozzle, primary aerosol built in a four-necked round-bottom flask, through a riser-pipe secondary arosol (smaller particle size) reached the test chamber
- Method of particle size determination: The determination of the particle size was not possible as teh substance was mainly emitted as gas.

TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatography with FID detector
- Samples taken from breathing zone: yes


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: not given
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): not given

Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
13.5 mg/L
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations 2/day; weights on Days 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: no other examinations
Statistics:
Single exposure concentration - no statistics presented.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 13 500 mg/m³ air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Taking into account that the measured concentration (13.5 mg/L) greatly exceeds the saturated vapour concentration (7.19 mg/L), the exposure atmosphere is considered a mixture of saturated vapour and aerosol.
Mortality:
1/5 males; 0/5 females
Clinical signs:
other: Ataxia, irregular respiration, stupor, altered gait, prostration, tonic convulsions, trembling and reduced spontaneous activity were seen in both sexes during the 14-day observation period.
Body weight:
No treatment-related effect identified.
Gross pathology:
1/5 males had dark red, patchy lungs. [The extent of examination is unclear.]

Table 1: Concentration and mortality per animals treated

Analytical Conc. (mg/L)

Mortality (dead/total)

Males

Females

Combined

13.5

1/5

0/5

1/10

Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
In an acute inhalation (vapour) study conducted in compliance with OECD 403 and GLP (reliability score 1) in which rats were exposed to triethoxy(methyl)silane at a concentration of 13.5 mg/L for four hours only one animal from a total of ten died. The LC50 thus is greater than 13.5 mg/L (highest achievable dose).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
13 500 mg/m³
Quality of whole database:
The study was conducted according to an appropriate OECD test guideline and in compliance with GLP. Nevertheless the determination of the particle size failed, presumably because the substance was emitted mainly as vapour.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16.09.1991 to 10.03.1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Iffa-Crédo, FRANCE
- Age at study initiation: 6-8 wk
- Weight at study initiation: 212-259 g (variability within sex <20%)
- Fasting period before study: none specified
- Housing: 1/F1 polycarbonate cage
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): at least 8
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1991-11-18 To: 1991-12-03
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back and flanks
- % coverage: approx 10%
- Type of wrap if used: semi-occlusive (perforated adhesive band/elastic crepe bandage)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with Codex absorbant gauze
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2007 mg/kg bw (2.23 mL/kg bw)
- Concentration (if solution): neat liquid
Duration of exposure:
24 h
Doses:
2007 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation at 0 and 15 mins, 1, 2 and 4 h, then daily until study completion at 15 days; weighting on Days 0, 8 and 15. The daily observations performed, amongst others, included changes in the fur, in the treated skin, the eyes, mucous membranes, respiratory system, circulatory system, autonomic and central nervous systems, as well as somato-motor activity and behaviour. Shivering, convulsions, salivation, diarhoea, lethargy, sleeping and coma were noted with particular attention.
- Necropsy of survivors performed: yes, on Day 15 all rats were killed and necropsied. Particular attention was paid to liver, heart, kidneys, lungs and skin of application site.
- Other: Cutaneous lesions were evaluated daily for each rat from Days 2 to 15, according to a scale equivalent to that of Draize.
Statistics:
The body weights of the animals were evaluated for each sex, calculating the mean of the values obtained, the standard deviation, the coefficient of variation which indicates the homogeneity of the data.

As no deaths were observed an LD50 could not be calculated.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 007 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no deaths, no clinical effects
Mortality:
0/10
Clinical signs:
No effects reported.
Body weight:
No treatment-related effects reported.
Gross pathology:
No abnormal observations.
Other findings:
No local effects (erythema or oedema).

Table1. Number of animals dead and with evident toxicity

 Dose

(mg/kg bw)

Mortality dead/total)

Number with evident toxicity (/total)

Male

Female

Combined

Male

Female

Combined

2007

0/5

0/5

0/10

0/5

0/5

0/10

 

Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
In an acute dermal toxicity study conducted in compliance with OECD 402 and in accordance with GLP (reliability score 1), there were no mortality or other adverse effects observed at 2007 mg/kg bw. (24 hour exposure) (LD0 and LD50 > 2007 mg/kg bw).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 007 mg/kg bw
Quality of whole database:
The study was conducted according to an appropriate OECD test guideline, and in compliance with GLP.

Additional information

Studies were chosen as key when the available study was of relevance and sufficient quality for classification, labelling and risk assessment. Other available data are included as supporting studies.

The key acute oral toxicity study which was conducted in compliance with GLP and according to the now deleted OECD TG 401, reports an LD50 value of >2007 mg/kg bw for triethoxy(methyl)silane. There were no mortality or marked systemic effect in rats at the limit dose of 2007 mg/kg bw (Hazleton France, 1992a). A supporting acute oral toxicity study conducted without compliance to GLP and similar to OECD TG 401 was also available on triethoxy(methyl)silane, which reported oral LD50 values of 7627 and 10057 mg/kg bw (dose given in mL/kg, converted using a relative density of 0.89), for males and females, respectively (Bushy Run Research Centre, 1981). A second supporting acute oral toxicity study conducted with triethoxy(methyl)silane according to OECD TG 423 in compliance with GLP reported a LD50 > 2000 mg/kg bw for female rats (METI, 2011). The results of all three experiments are in agreement with the low acute oral toxicity potential of triethoxy(methyl)silane.

 

The key acute inhalation toxicity study which was conducted in compliance with GLP and according to OECD TG 403 reports an LC50 of >13500 mg/m³ for triethoxy(methyl)silane vapour in rats after 4 hours. One animal from a total of ten died. The study reported that it was technically not possible to determine the particle size, presumably because the substance was emitted mainly as vapour. It was not stated whether the tested concentration was the highest achievable concentration, but taking into account that the measured concentration (13.5 mg/L) greatly exceeds the saturated vapour concentration (Hoechst, AG 1991). A limited report of an acute inhalation toxicity study without guideline compliance or GLP was also available, which reports one death in ten rats following a 6-hour exposure to the 'substantially saturated vapour’ of triethoxy(methyl)silane (Bushy Run Research Center, 1981). The exposed concentration was not given; however, this study further supports the lack of acute toxicity by the inhalation route of triethoxy(methyl)silane.

 

The key acute dermal toxicity study which was conducted in compliance with GLP and according to OCED TG 402, reports an LD50 value of >2007 mg/kg bw for triethoxy(methyl)silane. There were no mortality or marked systemic effect in rats at the limit dose of 2007 mg/kg bw (24 hour exposure) (Hazelton France, 1992b). A supporting acute dermal toxicity study which was not compliant with GLP but conducted in accordance with generally accepted scientific standards was also available, which reports an LD50 value of 11837 mg/kg (males) and >14240 mg/kg (females) (dose given in ml/kg, converted using a relative density of 0.89) (Bushy Run Research Center, 1981) thereby, further supporting the lack of acute toxicity potential by the dermal route of triethoxy(methyl)silane.


Justification for classification or non-classification

The available data on acute toxicity of the registered substance do not meet the criteria for classification according to Regulation 1272/2008 and are therefore conclusive but not sufficient for classification.